Special mechanisms of mutation are induced in bacteria, yeast and human cells under growth-limiting stress, under the control of stress responses. These mechanisms increase genetic diversity and potentially the ability to evolve specifically when cells are maladapted to their environment, i.e., when they are stressed. Stress-synchronous- mutation mechanisms may provide superior models for genetic changes that drive pathogen-host adaptation, antibiotic resistance, aging, cancer progression and therapy- resistance mechanisms, and possibly much of evolution generally. This project is an investigation of three molecular mechanisms of stress-synchronous genomic instability in E. coli, with a goal of finding common themes. Because the mechanisms studied have common components with several other (less understood) mechanisms of stress- synchronous mutation, the results should provide both important models for understanding the problems listed above and specific tools for combating antibiotic resistance. PUBLIC HEALTH RELEVANCE: This project will provide new ways to approach and combat problems of development of cancers, evolution of cancer-chemotherapy resistance, aging, microbial pathogenesis and antibiotic resistance among other serious problems in human health.